This study is the first to report the clinical features of glaucoma associated with a TANK binding kinase (TBK1) gene duplication.

Study design

In this retrospective, observational case series, researchers assessed 7 members (14 eyes) of a pedigree with a TBK1 gene duplication. Clinical features such as IOP, central corneal thickness (CCT), optic nerve head appearance and Humphrey visual field findings were followed from diagnosis to the latest follow-up (March 1985–May 2018).

Outcomes

Mean age at time of diagnosis was 35 (range 22–46 years), with an IOP of 21 mm Hg or less at presentation and throughout follow-up; the average initial IOP was 16 mm Hg. The average CCT was 506 μm (range 463–541 μm) and the average cup-to-disc ratio was 0.9 (range 0.8–0.99). At the initial visit, 1 eye met the criteria for legal blindness. The first visual field mean deviation was, on average, -9.0, with 29% of eyes having no field defects, 29% with early field defects and 43% with severe field defects.

Topical medication, laser trabeculoplasty and/or trabeculectomy led to a mean 28% IOP reduction in 3 eyes. None of the family members had fast progression (>1 dB/year). Four eyes (33%) had stable visual fields with a 22% reduction in IOP. Three eyes (25%) had slow progression (<0.5 dB/year) with a 45% IOP reduction. Two of these eyes progressed despite having an IOP of 10 mm Hg or less. Five eyes (42%) progressed at a moderate rate (0.5–1 dB/year) and demonstrated a 30.5% IOP reduction; 3 of these eyes received trabeculectomies.

Limitations

This study is limited by its small sample size and gaps in follow-up visits.

Clinical significance

This study presents a few clinical points. Physicians must be more cautious and observant when managing young patients with glaucoma. Despite slow progression in this subgroup, this progression can become clinically significant when following a young patient over decades. Genetic mutations and family history must also be considered in this patient population. Finally, based on stabilized disease in 1 case in which IOP reduced to 10 mm Hg or less, lower IOP may slow disease progression.